Mok Hyejung, Park Ji Won, Park Tae Gwan
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Korea.
Bioconjug Chem. 2008 Apr;19(4):797-801. doi: 10.1021/bc700464m. Epub 2008 Mar 26.
Quantum dot (QD) and adenovirus (ADV) nanoparticles were surface-modified with graft copolymers that exhibited a charge reversal behavior under acidic condition. Poly(L-lysine) (PLL) was grafted with multiple biotin-PEG chains (biotin-PEG-PLL graft copolymer), and the remaining primary amine groups in the PLL backbone were postmodified using citraconic anhydride, a pH-sensitive primary amine blocker, to generate carboxylate groups. The surfaces of streptavidin-conjugated QDs were modified with citraconylated biotin-PEG-PLL copolymer, producing net negatively charged QD nanoparticles. Under acidic conditions, citraconylated amide linkages were cleaved, resulting in the recovery of positively charged amine groups with subsequent alteration of surface charge values. Intracellular delivery of QD nanoparticles was greatly enhanced in an acidic pH condition due to the surface charge reversal. The surface of avidin-conjugated adenovirus (ADV-Avi) encoding an exogenous green fluorescent protein (GFP) gene was also modified in the same fashion. The expression extent of GFP was significantly increased at more acidic pH than pH 7.4. This study demonstrates that various nanosized drug carriers, imaging agents, and viruses could be surface-engineered to enhance their cellular uptake specifically at a low pH microenvironment like solid tumor tissue.
量子点（QD）和腺病毒（ADV）纳米颗粒用接枝共聚物进行了表面修饰，该接枝共聚物在酸性条件下表现出电荷反转行为。聚（L-赖氨酸）（PLL）接枝了多条生物素-聚乙二醇链（生物素-聚乙二醇-PLL接枝共聚物），PLL主链中剩余的伯胺基团用柠康酸酐（一种pH敏感的伯胺封闭剂）进行后修饰，以生成羧基。链霉亲和素偶联的量子点表面用柠康酸化的生物素-聚乙二醇-PLL共聚物进行修饰，产生带净负电荷的量子点纳米颗粒。在酸性条件下，柠康酸化的酰胺键被裂解，导致带正电荷的胺基团恢复，随后表面电荷值发生改变。由于表面电荷反转，在酸性pH条件下，量子点纳米颗粒的细胞内递送大大增强。编码外源性绿色荧光蛋白（GFP）基因的抗生物素蛋白偶联腺病毒（ADV-Avi）的表面也以同样的方式进行修饰。在比pH 7.4更酸性的pH条件下，GFP的表达程度显著增加。这项研究表明，各种纳米尺寸的药物载体、成像剂和病毒可以进行表面工程改造，以在低pH微环境（如实体瘤组织）中特异性增强它们的细胞摄取。
